HIV is becoming more of a chronic disease to manage with continuing treatment advancements. While this is particularly encouraging, it poses increased opportunities for HIV transmission, due to individuals living longer with the infectious disease. The development of evidence-based interventions for populations with HIV to reduce new infections has been somewhat limited in scope, and very few of those interventions have incorporated the environment in which individuals live as a determinant of high-risk behaviors. Individual behavior change seems additionally challenging to sustain considering the environmental factors in which a large proportion of individuals with HIV live;as has been found in smoking cessation, where individuals are more successful when worksite and home smoking bans are in effect. Alcohol and illicit drug use have been shown to be proximally and distally related to HIV transmission and sexually transmitted infections (STI) due to unplanned and unprotected sexual behavior as well as needle sharing or sharing pipes with open sores among drug use partners. Higher rates of alcohol use have been associated in neighborhoods with higher density of alcohol-selling establishments as well as marketing of alcohol using billboards. Types and frequency of drug use and rates of STIs have been shown to vary by neighborhood. Furthermore, there have been few studies that found faster HIV progression occurring in low-income neighborhoods. Sexual behaviors have been found to be less risky after HIV diagnosis;yet STI incidence rates continue, which urges the need for improved prevention efforts. Engagement in high-risk behaviors is clearly continuing among individuals with HIV and more effective interventions are necessary to stop the transmission of HIV. Individual- level risk reduction efforts have not yet been broadly successful. Finding neighborhood factors that influence high risk behaviors among individuals with HIV may help develop appropriate interventions. This study aims to examine the geographic distribution of illicit drug using behaviors, alcohol consumption, and sexual risk behaviors among individuals with HIV in 4 U.S. metropolitan areas across 7 different HIV clinics. These findings will also reveal opportunities for neighborhood-based interventions aimed to reduce HIV transmission. This study is being proposed as an opportunity to repurpose data from the established Centers for Disease Control and Prevention (CDC)-funded multi-site Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy. Specifically, this study aims to: (1) develop a multilevel model of risk behaviors (illicit drug and alcohol use, sexual behaviors) among 700 individuals with HIV in a multi-city (St. Louis, MO;Minneapolis, MN;Denver, CO;and Providence, RI) sample using individual interviews and GIS, and (2) develop a spatial model of high-risk behavior environments among individuals with HIV in the 4 metropolitan areas that can explain geographic differences high-risk behaviors among individuals with HIV and identify areas where interventions could be implemented. PUBLIC HEALTH RELEVANCE: This study aims to assess the role of the neighborhood on engagement in high-risk behaviors, including illicit drug and alcohol use and unprotected sexual behaviors as they contribute to the transmission of HIV. We have proposed a study that represents a sample of individuals with HIV who are engaged in care in 4 U.S. metropolitan areas across 7 clinics. Prevention efforts in the U.S. have had limited effectiveness, with consistent rates of HIV incident cases annually. Understanding the environmental context in which HIV transmission behaviors occur among infected populations will enhance the opportunities to identify new and appropriate areas of intervention to prevent HIV transmission. These findings will impact clinic practices and overall HIV prevention efforts in the U.S.